Depletion of PDGF from serum inhibits growth of AIDS-related and sporadic Kaposi's sarcoma cells in culture.

We have examined the mitogenic potential of platelet-derived growth factor (PDGF) on AIDS (acquired immune deficiency syndrome)-related and sporadic Kaposi's sarcoma cells in comparison to fibroblasts at physiological and subphysiological calcium concentrations of the culture medium. At low calcium concentrations in the presence of 3% human serum the growth rate of fibroblasts and Kaposi's sarcoma (KS) cells is similarly reduced to less than half of the growth rate at physiological Ca2+ concentrations. In the presence of 3% PDGF depleted, platelet poor plasma-derived serum (PPPS) growth of KS cells ceased completely, whereas fibroblasts made 1-2 cell divisions within 15 days. At physiological Ca2+ concentrations, the reduced PDGF content in 3% PPPS had no effect on human embryonal fibroblasts and little effect on adult skin fibroblasts. In contrast, KS cells became growth-arrested after one to two doublings. This is consistent with the observation that PDGF B-chain mRNA could not be detected in our KS cells whereas PDGF receptor mRNA was expressed.

Tumor necrosis factor alpha induces invasiveness of human skin fibroblasts in vitro.

The chemotactic response of fibroblasts plays an important role during wound healing and fibrosis. Several substances have been found to mediate fibroblast migration in vitro. In the tissue, however, fibroblasts have also the potential to pass through connective tissue barriers following a chemotactic stimulus. Since tumor necrosis factor alpha (TNF alpha) is a cytokine released by mononuclear cells during wound healing, we have been interested in studying its effect on the regulation of fibroblast chemotaxis and invasive migration. TNF alpha did not attract skin fibroblasts nor did it alter their chemotactic response towards other chemoattractants like fibroblast conditioned medium or fibronectin. However, whereas normal skin fibroblasts did not invade a collagen I gel, preincubation of the cells with TNF alpha markedly induced their invasive migration into the gel. This seems to be associated with a specific degradation of type I collagen, because TNF alpha did not promote the invasion of skin fibroblasts through a reconstituted basement membrane (Matrigel).

Increased adhesion of fibroblasts from patients with scleroderma to extracellular matrix components: in vitro modulation by IFN-gamma but not by TGF-beta.

A characteristic feature of systemic scleroderma is fibrosis of the skin and eventually of internal organs resulting from an overproduction of collagen and other connective tissue components by the resident fibroblasts. The balance between the cells and the amount of the surrounding extracellular matrix is then altered. Because cellular metabolism depends to a large extent on cellular contacts and communications with connective tissue molecules, we have therefore investigated the interactions with extracellular matrix components of fibroblasts obtained from skin of patients affected with scleroderma. In comparison to fibroblasts from healthy skin, all fibroblasts from scleroderma patients had an increased adhesion capacity to collagens I, IV, VI, fibronectin, and laminin. In addition, whereas adhesion of control fibroblasts was stimulated by a pre-treatment with transforming growth factor-beta, adhesion patterns of scleroderma fibroblasts remained unchanged. However, pre-incubation of the cells with interferon-gamma decreased the adhesion of both scleroderma and control fibroblasts.

Effects of enprofylline on A1 and A2 adenosine receptors.

The effects of enprofylline were studied on A1 adenosine receptors of rat fat cells and on A2 adenosine receptors of human platelets and of guinea-pig lung. Enprofylline antagonized the 5'-N-ethylcarboxamidoadenosine (NECA)-induced stimulation of platelet adenylate cyclase activity with a KB of 130 microM. In human platelets, enprofylline did not antagonize but potentiated the NECA-induced inhibition of aggregation. This potentiation was abolished in the presence of the phosphodiesterase inhibitor papaverine. An adenosine antagonistic effect of enprofylline could not be evaluated on A2 receptors of guinea-pig lung because the xanthine enhanced basal and NECA-stimulated cyclic AMP accumulation. Enprofylline antagonized the N6-R-(-)-phenylisopropyladenosine (R-PIA)-induced inhibition of rat fat cell adenylate cyclase with a KB of 32 microM. The Ki value for inhibition of [3H]PIA binding to fat cell membranes was 45 microM. Enprofylline inhibited cyclic AMP phosphodiesterase activity of human platelets, guinea-pig lung and rat fat cells with Ki values of 15, 130 and 110 microM, respectively. The results show that enprofylline was nearly equipotent as antagonist at A1 and A2 adenosine receptors. Mechanisms other than adenosine antagonism or phosphodiesterase inhibition may be involved in the pharmacological effects of enprofylline.

Evidence for an A2 adenosine receptor in guinea pig lung.

Adenosine receptors in guinea pig lung were characterized by measurement of cyclic AMP formation and radioligand binding. 5'-N-Ethylcarboxamidoadenosine (NECA) increased cyclic AMP levels in lung slices about 4-fold over basal values with an EC50 of 0.32 mumol/l. N6-R-(-)-Phenylisopropyladenosine (R-PIA) was 5-fold less potent than NECA. 5'-N-Methylcarboxamidoadenosine (MECA) and 2-chloroadenosine had EC50-values of 0.29 and 2.6 mumol/l, whereas adenosine and inosine had no effect. The adenosine receptors in guinea pig lung can therefore be classified as A2 receptors. Several xanthine derivatives antagonized the NECA-induced increase in cyclic AMP levels. 1,3-Diethyl-8-phenylxanthine (DPX; Ki 0.14 mumol/l) was the most potent analogue, followed by 8-phenyltheophylline (Ki 0.55 mumol/l), 3-isobutyl-1-methylxanthine (IBMX; Ki 2.9 mumol/l) and theophylline (Ki 8.1 mumol/l). In contrast, enprofylline (1 mmol/l) enhanced basal and NECA-stimulated cyclic AMP formation. In addition, we attempted to characterize these receptors in binding studies with [3H] NECA. The KD for [3H]NECA was 0.25 mumol/l and the maximal number of binding sites was 12 pmol/mg protein. In competition experiments MECA (Ki 0.14 mumol/l) was the most potent inhibitor of [3H]NECA binding, followed by NECA (Ki 0.19 mumol/l) and 2-chloroadenosine (Ki 1.4 mumol/l). These results correlate well with the EC50-values for cyclic AMP formation in lung slices. However, the Ki-values of R-PIA and theophylline were 240 and 270 mumol/l, and DPX and 8-phenyltheophylline did not compete for [3H] NECA binding sites. Therefore, a complete characterization of A2 adenosine receptors by [3H]NECA binding was not achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

[Angiolymphoid hyperplasia with eosinophils. Case report and differentiation from Kimura disease]. / Angiolymphoide Hyperplasie mit Eosinophilen. Fallbericht und Abgrenzung gegenüber dem Morbus Kimura.

We report a 40-year-old patient, who presented with a nodular tumor at the scalp. The histological diagnosis was angiolymphoid hyperplasia with eosinophils (ALHE). Immunohistochemical staining of the proliferating vessels was characteristic for endothelial cells. The perivascular inflammatory infiltrate mainly consisted of CD4-positive lymphocytes. Recently it has become clear that Kimura disease, which was thought to be a variant of ALHE, can be distinguished from ALHE by clinical, histological and immunohistochemical criteria and constitutes its own clinical identity. While ALHE is a localized proliferation of endothelial cells, Kimura disease is a proliferation of lymphoid cells characterized by invasive growth and possibly lymphadenopathy.

[Lichen ruber hypertrophicus with verrucous carcinoma]. / Lichen ruber hypertrophicus mit verrukösem Karzinom.

A 51-year-old patient presented with aggregated papules and with a central, partly erosive plaque on the left lower leg. Histological examination revealed hypertrophic lichen planus peripherally and a verrucous carcinoma within the centre. The lesion was removed surgically. Shortly after wards an atrophic lichen planus developed exclusively within the skin graft, which was effectively treated with topical steroid cream. The patient remained disease-free for 2 years. The literature relating to malignant transformation of cutaneous lichen planus was reviewed. In most cases, as in the present one, the hypertrophic form of lichen planus and the verrucous type of carcinoma (Ackerman) are reported. Recent investigations have revealed human papilloma virus types 6 and 11 within such lesions.

[Tumor of the follicular infundibulum. Study of determining follicular differentiation]. / Tumor des follikulären Infundibulums. Untersuchung zur Bestimmung der follikulären Differenzierung.

Tumor of the follicular infundibulum is a rare proliferation of cells and its histogenesis or differentiation at the morphological level has been the subject of some controversy. In recent years cytokeratins have been recognized as important markers of epithelial differentiation, and of late new retrieval methods have meant it is possible to detect them in formalin-fixed and paraffin-embedded tissue. Four patients were studied, the ages ranging between the 2nd and 7th decade. The tumors were all located in the head and neck and in one case the lesion developed in a pre-existing sebaceous nevus. The morphological investigation revealed a flat, proliferation of polygonal, pale eosinophilic cells connected to epidermis or follicular infundibulum and with a centrally located nucleus. In addition, a few ductal structures resembling sebaceous ducts were seen and in one case a hair germ papilla and a follicular papilla was noted. Immunohistochemical investigations with antibodies against cytokeratins revealed differentiation comparable to that in the fetal follicular isthmus and, in one case, also differentiation in keeping with the fetal follicular infundibulum.

[Torus mandibularis]. / Torus mandibularis.

Solitary or bilateral, symptomless exostoses on the lingual surface of the mandibule are called mandibular torus. It is mainly seen in young males and has a benign clinical course. The etiopathology is not known. Both genetic and environmental factors such as the anatomy of the lower jaw are considered. Syndromes associated with facial exostoses such as Proteus syndrome or Gardner's syndrome should be clinically excluded. A 40-year-old man with exostoses of the jaw is reported. With this case report we would like to draw attention to a disease which has rarely been described in the German dermatological literature.

[Immunogenetic findings in herpes gestationis]. / Immungenetische Befunde bei Herpes gestationis.

A 27-year-old woman suffered from herpes gestationis in her second pregnancy. The pruricy urticarial and bullous skin lesions were exacerbated immediately after birth, and premenstrually after the onset of menstruation. The diagnosis was confirmed by the determination of anti-basement membrane antibodies of the IgG class both in the serum (herpes gestationis factor) and in lesional skin by immunofluorescence techniques. The newborn had no skin lesions and no basement membrane zone antibodies were detected. The HLA (human leucocyte antigen) typing revealed the HLA-A11/1, B18/w63, C-/-, DR4/w13, DQw3/w1 haplotype in the mother and the HLA-A3/31, B7/35, Cw7/w4, DR2/3, DQw1/w2 haplotype in the father. Comparison with the first child (HLA-A11/31, B18/35, -/Cw4, DR4/3, DQw3/w2) showed that the second child (HLA-A11/3, B18/7, -/Cw7, DR4/2, DQw3/w1) had a different HLA haplotype. The pattern of the HLA haplotype of the mother and the father seems to be important in the immunopathogenesis of herpes gestationis.

[Multiple disseminated glomus tumors (glomangioma). Immunohistochemical analysis and differentiation from viscerocutaneous hemangiomatosis]. / Multiple disseminierte Glomustumoren (Glomangiome). Immunhistochemische Analyse und Abgrenzung zur viszerokutanen Hämangiomatose.

A 25-year-old patient presented with multiple disseminated asymptomatic bluish nodules, which had been present since childhood. Histological examination revealed vascular cavities surrounded by round to oval eosinophilic cells. Positive immunohistochemical staining with alpha-smooth-muscle antigen (alpha-SMA) and vimentin confirmed the diagnosis of multiple disseminated glomus tumours of the vascular type. Tumour cells were surrounded by a network of type IV collagen. In contrast antibodies against the intermediate filament protein desmin and the endothelial markers BMA 120 and anti-von Willebrand factor revealed no staining of the glomus cells. This was the first immunohistochemical investigation of a glomus tumour of vascular type. Immunohistochemical staining of these glomus cells revealed no difference from other histological types of glomus tumours.

["Baboon syndrome". A particular manifestation of hematogenous contact reaction]. / Das "Baboon-Syndrom". Eine besondere Manifestation einer hämatogenen Kontaktreaktion.

We report on a 52-year-old patient with a typical manifestation of a haematogenous contact reaction. The characteristic distribution of light-red erythema predominantly located in the major flexural areas of the extremities and on the buttocks was consistent with the diagnosis of "baboon syndrome." The term derives from the skin lesions, which are compared to the red gluteal region of the baboon. An allergic type-IV reaction to systemically administered allergens probably underlies lesions of this type. In our case the baboon syndrome had been induced by amoxicillin. So far, mercury, nickel, ampicillin, and heparin have been reported as causes of baboon syndrome.

[Papular mucinosis. A rare cutaneous manifestation of lupus erythematosus]. / Die papulöse Muzinose. Eine seltene kutane Manifestation des Lupus erythematodes.

The case of a 48-year-old patient with systemic lupus erythematosus is discussed. Under immunosuppressive therapy, symptomless papules occurred on the shoulders, back, chest and face. Histologically, there were deposits of mucinous matter which produced an intensive blue colour in the HALE-PAS and alcian blue colour test. The epidermal and dermal inflammatory changes which typically occur with lupus erythematosus were absent. Whereas mucin is commonly diagnosed in lupus erythematosus, the clinical manifestation of papulous mucinosis is a rare but diagnostically significant phenomenon, since it can occur without further findings which are typical of lupus erythematosus.

[Atrophodermia linearis Moulin. A new disease picture, following the Blaschko lines]. / Atrophodermia linearis Moulin. Ein neues Krankheitsbild, das den Blaschko-Linien folgt.

Many different congenital and acquired skin diseases are seen along Blaschko's lines. In 1992, Moulin et al. [40] described five patients affected with a new clinical entity characterized by acquired atrophic band-like skin lesions showing hyperpigmentation. We report on a further patient with this skin disease. Characteristic features are hyperpigmented atrophoderma arranged in a pattern following the lines of Blaschko, with no preceding inflammation and no subsequent induration or scleroderma. The lesions usually appear during childhood or adolescence, but sometimes in young adults. For this skin disease we propose the term 'linear atrophoderma of Moulin'.

[Panfolliculoma. Clinical and immunohistochemical findings in 4 cases]. / Das Panfollikulom. Klinische und immunhistochemische Befunde von 4 Fällen.

Panfolliculoma is a rare benign neoplasm showing morphological similarities to the trichogenic trichoblastoma of Headington and the trichoblastoma of Ackerman. Eight patients have been previously reported; we add four additional patients. Their ages ranged from the 2nd to the 6th decade. The neoplasms were primarily situated on the head and the trunk. Clinical examination revealed a skin colored or red, dermal cystic nodule. The histological appearance of the panfolliculoma was characterized by symmetry, sharp circumscription and regular aggregations of cells, which were in parts solid or cystic. Additionally, follicular germs and papillae, matrical, inner and outer rooth sheath differentiation were identified. These varied forms of follicular differentiation were confirmed by the immunohistochemical expression of cytokeratins in different epithelial cells. Panfolliculoma is a benign neoplasm with proven morphological and immunhistochemical follicular differentiation.

A nevoid plaque with histological changes of trichoepithelioma and cylindroma in Brooke-Spiegler syndrome. An immunohistochemical study with cytokeratins.

Brooke-Spiegler syndrome is characterized by the development of multiple trichoepitheliomas and cylindromas. In addition, multiple spiradenomas have been observed in this autosomal-dominant inherited disease. We report a 53-year-old woman with multiple cylindromas on the head and neck and multiple trichoepitheliomas on the face. Additionally, she had had since birth a plaque on the right side of her neck containing two nodules with features of both cylindroma and trichoepithelioma. Immunohistochemical investigations revealed in the basaloid cells of trichoepithelioma an expression of CK 5/6, CK 14, CK 17, CK 19 and vimentin. The cells of the cylindroma lacked vimentin but expressed additionally CK 7, CK 8 and CK 18. The occurrence of cylindroma and trichoepithelioma in a single nevoid plaque from a patient with Brooke-Spiegler syndrome implies an alteration in the stem cells of the folliculosebaceous-apocrine unit and could be characteristic of the disorder.